CORRECTING and REPLACING MannKind Reports Positive Data from a Phase 3 Clinical Study of AFREZZA in Patients with Type 1

CORRECTING andREPLACING MannKind Reports Positive Data from a Phase 3
Clinical Study of AFREZZA in Patients with Type 1 Diabetes
CORRECTION…by MannKind Corporation
Business Wire
VALENCIA, Calif. -- August 14, 2013
Second graph under Other Results subhead, second sentence should read: The
event rate of severe hypoglycemia was also lower in the AFREZZA-Gen2 group
(8.05 events per 100 subject-months) than in the insulin aspart group (14.45
events per 100 subject-months); however, this difference was not statistically
significant (p=0.1022) (sted The event rate of severe hypoglycemia was also
lower in the AFREZZA-Gen2 group (8.05 events per subject-month) than in the
insulin aspart group (14.45 events per subject-month); however, this
difference was not statistically significant (p=0.1022)).
The corrected release reads:
MANNKIND REPORTS POSITIVE DATA FROM A PHASE 3 CLINICAL STUDY OF AFREZZA IN
PATIENTS WITH TYPE 1 DIABETES
MannKind Corporation (Nasdaq: MNKD) today announced positive preliminary
results from Study 171, a Phase 3 clinical study of AFREZZA^® (insulin human
[rDNA origin]) Inhalation Powder, an investigational, ultra rapid-acting
mealtime insulin therapy, administered using MannKind’s next-generation (Gen2)
inhaler (also known as the Dreamboat™ inhaler), in patients with type 1
diabetes.
Highlights
AFREZZA-Gen2, compared to insulin aspart, showed:
*Non-inferior decreases in A1c levels;
*Significantly less hypoglycemia;
*Significant decreases in fasting blood glucose levels; and
*Significant weight advantage.
In addition, the changes in pulmonary function observed in the AFREZZA-Gen2
group were no different than those observed in an AFREZZA treatment group that
utilized MannKind’s first-generation (MedTone) inhaler. This finding will
facilitate bridging the Gen2 inhaler to the pulmonary safety data that was
collected in earlier clinical studies using the MedTone inhaler.
“We are pleased that Study 171 met its primary endpoint of non-inferiority, by
demonstrating that AFREZZA produces A1c reductions comparable to insulin
aspart,” stated Alfred Mann, Chairman and Chief Executive Officer of MannKind
Corporation. “Importantly, this study also established a bridge between the
Gen2 inhaler and the large body of pulmonary safety data that was previously
collected for AFREZZA using the MedTone inhaler. Consistent with previous
studies of AFREZZA, including a two-year safety study involving 2,035
subjects, the use of AFREZZA was associated with a clinically insignificant
decrease in lung function that appeared at the onset of therapy, did not
progress during therapy and resolved fully upon cessation of therapy. Based on
the results of this study, we believe that AFREZZA can be used to achieve
glycemic control that is comparable to the current standard of care while at
the same time offering potential advantages in terms of lower fasting blood
glucose levels, weight neutrality and a lower overall risk of hypoglycemia.”
Study 171
Study 171 was an open-label study involving 518 patients with type 1 diabetes
on basal/bolus insulin therapy who were studied at sites in the United States,
Russia, Ukraine and Brazil. After a four-week run-in period to optimize their
basal insulin, patients entered a 24-week treatment period in which they were
randomized in one of three ways:
*Continuing on subcutaneous insulin aspart in combination with a basal
insulin (170 patients);
*Switching to AFREZZA administered using the Gen2 inhaler in combination
with their basal insulin (174 patients); or
*Switching to AFREZZA administered using the MedTone inhaler in combination
with their basal insulin (174 patients).
The treatment period consisted of 12 weeks of prandial insulin optimization
with continued basal titration followed by a 12-week period during which
subjects maintained stable doses of insulin (prandial and basal). There was
also a follow-up visit four weeks after completion of the treatment period.
Over the 24-week treatment period of this study, A1c levels decreased
comparably in the AFREZZA-Gen2 group (-0.21%) and the insulin aspart group
(-0.40%). The 95% confidence interval (0.02% to 0.36%) of the between-group
difference did not exceed the predetermined threshold of 0.40%, thereby
establishing non-inferiority between AFREZZA-Gen2 and insulin aspart, which
was the primary endpoint of the study.
Other Results
There was a significant difference in fasting blood glucose (FBG) levels in
the AFREZZA-Gen2 group compared to the insulin aspart group. In the
AFREZZA-Gen2 group, mean FBG levels decreased by 25.3 mg/dL by the end of the
treatment period whereas the insulin aspart group experienced an increase of
10.2 mg/dL in FBG levels over the same period (p=0.0027). After the four-week
follow-up period, during which all patients received insulin aspart and a
basal insulin, there was no longer any difference in FBG levels between the
treatment groups, demonstrating that this effect on FBG levels was
attributable to AFREZZA therapy.
Significantly less total hypoglycemia was observed in the AFREZZA-Gen2 group
(9.80 events per subject-month) compared to the insulin aspart group (13.97
events per subject-month; p<0.0001). The event rate of severe hypoglycemia was
also lower in the AFREZZA-Gen2 group (8.05 events per 100 subject-months) than
in the insulin aspart group (14.45 events per 100 subject-months); however,
this difference was not statistically significant (p=0.1022).
The proportion of subjects achieving A1c target levels ≤7.0% or ≤6.5% at the
end of the 24-week treatment period was less in the AFREZZA-Gen2 group than in
the insulin aspart group; however, among patients who achieved A1c levels
≤7.0% and ≤6.5% at the end of the 24-week treatment period, the event rates
for overall hypoglycemia (mild, moderate and severe) were all significantly
lower in the AFREZZA-Gen2 group than in the insulin aspart group.
There was also a significant difference in weight outcomes. Patients in the
AFREZZA-Gen2 group lost an average of 0.39 kg over the treatment period
compared to an average gain of 0.93 kg in the insulin aspart group (p=0.0102).
The main safety objective of this study was to compare changes in FEV[1]
(forced expiratory volume in one second) from randomization to week 24 between
the AFREZZA-Gen2 and AFREZZA-MedTone groups. Over this period, there was an
insignificant difference of 0.01 L in mean change in FEV[1] between the two
AFREZZA groups (p=0.5364). Over the same 24-week treatment period, the
decrease in FEV[1] seen in the AFREZZA-Gen2 group was slightly greater than
that seen in the aspart group (0.03 L). After cessation of the treatment
period, FEV[1] values in both AFREZZA groups increased, so that by the
follow-up visit at week 28 there were virtually no differences in FEV[1] among
the three treatment groups.
In general, treatment with AFREZZA was well-tolerated over 24 weeks by
subjects with type 1 diabetes. The incidence of serious adverse events related
to study drug was similar in the AFREZZA-Gen2 (2.3%), AFREZZA-MedTone (2.9%)
and insulin aspart (1.8%) groups. There were no serious cardiovascular events
reported in this study. The most common drug-related adverse event was cough,
reported by 30.5% of AFREZZA-Gen2 patients, 20.8% of AFREZZA-MedTone patients
and 0% of insulin aspart patients. Cough was predominantly dry, intermittent,
and usually occurred within 10 minutes of inhalation. The incidence of cough
was highest during the first week of the treatment period and diminished
quickly thereafter. The discontinuation rate due to cough was low
(AFREZZA-Gen2: 5.7%; AFREZZA-MedTone: 2.9%; insulin aspart: 0%).
These preliminary results are subject to further analysis.
About AFREZZA^®
AFREZZA^® is a novel, ultra rapid-acting mealtime insulin therapy being
developed by MannKind Corporation for the treatment of adult patients with
type 1 or type 2 diabetes for the control of hyperglycemia. It is a
drug-device combination product, consisting of AFREZZA Inhalation Powder,
pre-metered into single-use cartridges, and a light, discreet and easy-to-use
inhaler. Administered at the start of a meal, AFREZZA dissolves immediately
upon inhalation and delivers insulin quickly to the bloodstream. Peak insulin
levels are achieved within 12 to 14 minutes of administration, effectively
mimicking the release of meal-time insulin observed in healthy individuals,
but which is absent in patients with diabetes.
About MannKind Corporation
MannKind Corporation (Nasdaq: MNKD) focuses on the discovery, development and
commercialization of therapeutic products for patients with diseases such as
diabetes. Its lead product candidate, AFREZZA^®, has completed Phase 3
clinical trials. MannKind maintains a website at www.mannkindcorp.com to which
MannKind regularly posts copies of its press releases as well as additional
information about MannKind. Interested persons can subscribe on the MannKind
website to e-mail alerts that are sent automatically when MannKind issues
press releases, files its reports with the Securities and Exchange Commission
or posts certain other information to the website.
Forward-Looking Statements
This press release contains forward-looking statements, including statements
related to the results of clinical studies, the bridging to an earlier
clinical program, the potential use of AFREZZA to achieve glycemic control in
type 1 diabetes patients that is comparable to the current standard of care,
and the potential advantages of AFREZZA over current treatments, that involve
risks and uncertainties. Words such as "believes", "anticipates", "plans",
"expects", "intend", "will", "goal", "potential" and similar expressions are
intended to identify forward-looking statements. These forward-looking
statements are based upon the Company's current expectations. Actual results
and the timing of events could differ materially from those anticipated in
such forward-looking statements as a result of these risks and uncertainties,
which include, without limitation, difficulties or delays in obtaining
regulatory feedback or completing and analyzing the results of clinical
studies, completion of further statistical analysis of the results of Study
171, whether the data from Study 171, as well as Study 175, the Phase 3
clinical study of AFREZZA in type 2 diabetes patients, will satisfy all
requirements of the Food and Drug Administration and will be sufficient to
support approval of an amended new drug application for AFREZZA, the timing of
regulatory review and decisions, MannKind’s ability to manage its existing
cash resources or raise additional cash resources, stock price volatility and
other risks detailed in MannKind's filings with the Securities and Exchange
Commission, including the Annual Report on Form 10-K for the year ended
December 31, 2012 and periodic reports on Form 10-Q and Form 8-K. You are
cautioned not to place undue reliance on these forward-looking statements,
which speak only as of the date of this press release. All forward-looking
statements are qualified in their entirety by this cautionary statement, and
MannKind undertakes no obligation to revise or update any forward-looking
statements to reflect events or circumstances after the date of this press
release.
Contact:
MannKind Corporation
Matthew Pfeffer
Chief Financial Officer
661-775-5300
mpfeffer@mannkindcorp.com